Immunotherapy's potential for prostate cancer treatment

“I think immunotherapy is going to be a very important component of treatment [for prostate cancer] as we go into the future,” said Dr. Elahe Mostaghel, a clinical researcher at Fred Hutch.

Mostaghel envisions immunotherapies not, perhaps, as a cure for the disease, but as part of a combination strategy to slow the growth of the tumors so much that this cancer becomes a chronic disease rather than a life-threatening one.

“I think it’s going to be one of the most exciting and durable ways we’re going to have to treat prostate cancer,” she said.

Mostaghel highlighted three immunotherapy approaches that are furthest along in development for prostate cancer patients: an approved T cell-stimulating vaccine and two strategies — checkpoint inhibitor drugs and cell therapy — that are still experimental:

First is a therapeutic vaccine approach that turns on T cells to fight cancer cells. This strategy is already in the clinic, and many patients may be familiar with sipuleucel-T (better known by its brand name, Provenge), which is approved by the Food and Drug Administration for treating advanced prostate cancer. In this strategy, patients’ white blood cells are collected and exposed to a tumor protein to stimulate them before being returned to the patient’s bloodstream to activate tumor-specific T cells to kill cancer. Another strategy, still in trials, uses a harmless virus programmed with a bit of tumor DNA to activate patients’ immune cells.

Second, drugs known as checkpoint inhibitors are FDA-approved to treat a variety of cancers, including melanoma, bladder cancer, and Hodgkin lymphoma. Tumors are pros at shutting down cancer-killing immune responses. Checkpoint inhibitors work by blocking the “shutdown” signals, allowing immune cells to rev up to kill cancer cells. Although checkpoint inhibitors aren’t yet FDA-approved for prostate cancer, several ongoing clinical trials are testing them, especially in combination with standard prostate cancer drugs like the hormone blocker enzalutamide.

Third, and a bit further from the clinic, Mostaghel said, is an experimental strategy in which patients’ immune cells are genetically reprogrammed to kill cancers. The cells are weaponized with an artificial molecule known as a chimeric antigen receptor, or CAR, that enables immune cells to recognize and kill cancer cells.

This strategy, while still not approved by the FDA for any disease, “has shown efficacy in other tumors, and I think it just needs more time before it shows efficacy in prostate cancer,” Mostaghel said.

Exercise and prostate cancer survivorship

Regular exercise lowers your risk of developing many cancers, including cancer of the prostate. But if you’ve already developed prostate cancer, can exercise help?

Yes, said prostate cancer expert Dr. Jonathan Wright, a urologic oncologist at UW and a Hutch faculty member. The American Cancer Society recommends regular cardiovascular and strength training for all cancer survivors, and it advises that survivors return to regular physical activity as soon as possible after treatment. Exercise has been shown to have numerous benefits for men who are being treated for prostate cancer, from lowered anxiety to improved self-esteem — and large studies have also linked regular exercise to slowed prostate tumor growth and improved survival.

One example of exercise’s benefits in prostate cancer is for men on androgen-deprivation therapy, Wright said. This common treatment deprives prostate tumors of their fuel ― testosterone and related hormones ― but it can cause fatigue and other difficult side effects. A study published earlier this year showed that many different types of exercise help boost the energy level of men on long-term androgen-deprivation therapy. And the more fatigued the men were at the beginning of the yearlong study, the researchers found, the bigger the boost they got from exercising.

Research by Wright and others is ongoing to strengthen the evidence base for the benefits of exercise in prostate cancer. (See this trial and this one.) His hope is that doctors in the U.S. soon will be able to prescribe exercise for their patients with prostate cancer, just as patients with heart problems can be prescribed exercise-based rehabilitation. But first, Wright said, “We need the studies.”

Personalized care through genomics

Emerging data are beginning to paint a picture of how genetic testing could help doctors target therapies to the specific weaknesses of a given patient’s prostate cancer.

“Genetic testing will be increasing” in prostate cancer care, said Dr. Heather Cheng, the director of the Seattle Cancer Care Alliance Prostate Cancer Genetics Clinic, which opened in 2016. “We’re actively trying to maximize benefit, not only to patients but also to their family members.”

For example, Dr. Colin Pritchard and colleagues at UW Medicine developed a genetic testing service called UW-OncoPlex, which uses cutting-edge genetic-sequencing technologies (called next-generation sequencing) to characterize more than 200 actionable tumor genes ― “actionable” meaning that there are cancer drugs available that target them. Pritchard and colleagues are testing a version of UW-OncoPlex that’s optimized for prostate cancer, with promising early results, he said.

Among the many possible avenues for genetically targeted therapies in prostate cancer, said Pritchard, “perhaps most exciting” is in men with mutations in key genes that are involved in repairing damage to DNA ― “because we might already have therapies available.”

Mutations in DNA-repair genes are thought to make cancers particularly vulnerable to certain therapies, including drugs known as platinum chemotherapies and PARP inhibitors. (These drugs have been FDA-approved to treat patients with other cancers and are under active investigation for patients with prostate cancer.)

Mutations in these genes, which can be passed on from parent to child, are now known to occur in men with advanced prostate cancer at rates “much, much higher than anyone had previously thought,” Cheng said. She and colleagues are now studying treatment strategies for men with these inherited mutations and considering how to improve early cancer-detection strategies for their family members.

“We need to do larger trials to confirm this, but the preliminary data is promising,” Pritchard said.

New technology for prostate-cancer imaging

New technologies for imaging prostate tumors are in development to help doctors detect tumors more effectively and, perhaps, improve treatment outcomes, researchers at the symposium said.

One is a strategy known as “multiparametric MRI,” said Dr. Daniel Lin, IPCR director and chief of Urologic Oncology at UW. This complex MRI-imaging technique combines multiple different types of MRI phases to create a 3-D image of a prostate that highlights an area of likely tumor activity ― and indicates exactly where the doctor should place biopsy needles to collect tissue for analysis. This may help reduce the chance that a biopsy will miss a small tumor. The UW had the first multi-parametric MRI setup in the five-state Northwest region, Lin said, but the technology is now becoming more widely available.

Multiparametric MRI doesn’t yet replace standard-of-care biopsy techniques that use a large number of biopsies in a grid pattern to try to catch any cancerous areas. And it may turn out not to be useful or cost-effective for every man. “But stay tuned,” Lin said.

Researchers are also developing new imaging compounds for use in PET scans that are easier to use and more likely to detect cancers, and research is ongoing to determine whether such scans can improve patient outcomes by helping doctors plan treatments more appropriately, said Dr. Evan Yu, a medical oncologist who treats patients with prostate cancer at SCCA, Fred Hutch’s clinical care partner. PET, or positron emission tomography, uses radioactive dyes that are injected into the patient’s vein and then taken up into certain tissues, which are then revealed on scans. In 2016, the FDA approved a PET-scan technique using a radioactive molecule called FACBC that is taken up by prostate cancer cells to detect locally recurrent cancers. Yu expects FACBC PET scans to be available to patients locally as early as September.

“The IPCR is dedicated to bringing these novel imaging and therapeutic approaches to the Northwest,” Yu said.

Is clinical trial participation right for you?

All of the research above was developed through clinical trials that relied on volunteer participants. While patient volunteers are indispensable for moving medical research forward, it’s common for patients to be unfamiliar with clinical trials and have misconceptions about participating in them.

Sandy Thompson and Scott Atkinson once did. Both metastatic prostate cancer patients from Washington state, the men have now participated in many trials. They spoke on a panel at the symposium about their experiences.

“I found that clinical trials are not exactly what I thought they were,” Thompson said. Here’s what the two men learned:

First, clinical trials aren’t limited to patients who are out of all other options — trials are available to patients at all stages of disease. And participating in a clinical trial of a new therapy doesn’t mean that you have a 50-50 chance of getting just a placebo or “sugar pill” in lieu of treatment: Cancer clinical trials typically compare an experimental strategy with the standard of care for that disease. In many cases, trials are not blinded, meaning that the patient and his doctor know which treatment he receives.

Both Thompson and Atkinson found great personal meaning in the chance to help others by participating in research.

“I try to donate my data when I can to help people in the future,” Atkinson said. Because of the trials in which he and others are participating, he said, this cancer someday “will be something that people die with instead of because of.”

This desire to help others is common among trial participants, said Dr. Bruce Montgomery, clinical director of Genitourinary Medical Oncology at SCCA. Other pluses for many are access to investigational new drugs and the greater medical attention that often is a part of trial participation. However, Montgomery said, men should consider that any investigational treatment has unknown effects, research protocols often require many more clinic visits than would be required under standard of care and insurance may not cover the costs of an experimental therapy.

Clinical research does not always test new therapies; this category includes research ranging from studies of patients’ blood to develop new early-detection tests, to surveys asking about men’s experiences with cancer, to tests of new imaging modalities for visualizing tumors.

People interested in participating in clinical research can find trials on the government-sponsored database, clinicaltrials.gov. Men interested in prostate cancer trials through the Fred Hutch/University of Washington Cancer Consortium can find current listings on SCCA’s clinical trials website.

Trial participation “has been a wonderful journey for me,” Atkinson said. “I’d encourage anyone to talk to your oncologist to see if any trials would be right for you at your stage.”

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Susan Keown, a staff writer at Fred Hutchinson Cancer Research Center, has written about health and research topics for a variety of research institutions, including the National Institutes of Health and the Centers for Disease Control and Prevention. Reach her at skeown@fredhutch.org or on Twitter @sejkeown.

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